Evaluation of the Antifungal Efficacy of Microbial Chondroitin Sulfate Against Candida Species in an Experimental Rat Model of Vulvovaginal Candidiasis

Chondroitin sulfate (CS) is a glycosaminoglycan with various biological functions including antioxidant and anti-inflammatory effects. Candida species, particularly Candida albicans , are major pathogens involved vulvovaginal candidiasis (VVC), which affects a majority of women, and novel antifungal agents are needed due to the limitations of current treatments. This study evaluated the antifungal efficacy of microbial chondroitin sulfate (MCS), produced via recombinant Escherichia coli (C2987), in a rat model of VVC. MCS was biosynthesized via the pETM6-PACF-vgb plasmid harboring the kfoA , kfoC , kfoF , and vgb genes, and its structural integrity and composition were confirmed via NMR, HPLC, and FT-IR. VVC was induced in immunosuppressed, estrogen-treated Wistar albino rats, which were randomized into eight groups: noninfected control, infected control, cream base, nystatin, fenticonazole, and MCS at 0.1%, 0.5%, and 1%, respectively. Topical treatments were applied for seven days, and the vaginal fungal burden (CFU), the levels of cytokines (IL-4, IL-8, and IL-17), the levels of oxidative stress markers in rat serum (MDA and SOD), and histopathology were assessed. MCS produced a dose-dependent reduction in fungal burden, with 1% MCS achieving CFU reductions comparable to those of nystatin and fenticonazole. Significant decreases in IL-8 and IL-17 and a moderate reduction in IL-4 were detected in rat vaginal lavage fluid, indicating an anti-inflammatory shift. Histopathological examination revealed improved epithelial architecture and reduced inflammatory infiltration in the 0.5% and 1% MCS groups, although the inflammation scores did not reach statistical significance. Serum oxidative stress analysis revealed trends toward lower malondialdehyde (MDA) levels and higher superoxide dismutase (SOD) activity, but the differences were not statistically significant. These findings suggest that MCS is a promising nonanimal-derived topical antifungal agent with both antifungal and immunomodulatory potential, warranting further clinical investigation.